Systems and methods of providing modulation therapy without patient-perception of stimulation

ABSTRACT

A neuromodulation system and method of providing sub-threshold modulation therapy. Electrical modulation energy is delivered to a target tissue site of the patient at a programmed intensity value, thereby providing therapy to a patient without perception of stimulation. In response to an event, electrical modulation energy is delivered at incrementally increasing intensity values. At least one evoked compound action potential (eCAP) is sensed in a population of neurons at the target tissue site of the patient in response to the delivery of the electrical modulation energy at the incrementally increasing intensity values. One of the incrementally increased intensity values is selected based on the sensed eCAP(s). A decreased intensity value is automatically computed as a function of the selected intensity value. Electrical modulation energy is delivered to the target tissue site of the patient at the computed intensity value, thereby providing sub-threshold therapy to the patient.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.14/338,695, filed Jul. 23, 2014, which claims the benefit of priorityunder 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No.61/858,730, filed on Jul. 26, 2013, which is herein incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present inventions relate to tissue modulation systems, and moreparticularly, to programmable neuromodulation systems.

BACKGROUND

Implantable neuromodulation systems have proven therapeutic in a widevariety of diseases and disorders. Pacemakers and Implantable CardiacDefibrillators (ICDs) have proven highly effective in the treatment of anumber of cardiac conditions (e.g., arrhythmias). Spinal CordStimulation (SCS) systems have long been accepted as a therapeuticmodality for the treatment of chronic pain syndromes, and theapplication of tissue stimulation has begun to expand to additionalapplications such as angina pectoralis and incontinence. Deep BrainStimulation (DBS) has also been applied therapeutically for well over adecade for the treatment of refractory chronic pain syndromes, and DBShas also recently been applied in additional areas such as movementdisorders and epilepsy. Further, in recent investigations, PeripheralNerve Stimulation (PNS) systems have demonstrated efficacy in thetreatment of chronic pain syndromes and incontinence, and a number ofadditional applications are currently under investigation. Furthermore,Functional Electrical Stimulation (FES) systems have been applied torestore some functionality to paralyzed extremities in spinal cordinjury patients.

Each of these implantable neuromodulation systems typically includes atleast one neuromodulation lead implanted at the desired modulation siteand an Implantable Pulse Generator (IPG) implanted remotely from themodulation site, but coupled either directly to the neuromodulationlead(s), or indirectly to the neuromodulation lead(s) via one or morelead extensions. Thus, electrical pulses can be delivered from theneuromodulator to the electrodes carried by the neuromodulation lead(s)to stimulate or activate a volume of tissue in accordance with a set ofmodulation parameters and provide the desired efficacious therapy to thepatient. The neuromodulation system may further comprise a handheldremote control (RC) to remotely instruct the neuromodulator to generateelectrical modulation pulses in accordance with selected modulationparameters. The RC may, itself, be programmed by a technician attendingthe patient, for example, by using a Clinician's Programmer (CP), whichtypically includes a general purpose computer, such as a laptop, with aprogramming software package installed thereon.

Electrical modulation energy may be delivered from the neuromodulationdevice to the electrodes in the form of an electrical pulsed waveform.Thus, electrical modulation energy may be controllably delivered to theelectrodes to modulate neural tissue. The configuration of electrodesused to deliver electrical pulses to the targeted tissue constitutes anelectrode configuration, with the electrodes capable of beingselectively programmed to act as anodes (positive), cathodes (negative),or left off (zero). In other words, an electrode configurationrepresents the polarity being positive, negative, or zero. Otherparameters that may be controlled or varied include the amplitude,width, and rate of the electrical pulses provided through the electrodearray. Each electrode configuration, along with the electrical pulseparameters, can be referred to as a “modulation parameter set.”

With some neuromodulation systems, and in particular, those withindependently controlled current or voltage sources, the distribution ofthe current to the electrodes (including the case of the neuromodulationdevice, which may act as an electrode) may be varied such that thecurrent is supplied via numerous different electrode configurations. Indifferent configurations, the electrodes may provide current or voltagein different relative percentages of positive and negative current orvoltage to create different electrical current distributions (i.e.,fractionalized electrode configurations).

As briefly discussed above, an external control device can be used toinstruct the neuromodulation device to generate electrical pulses inaccordance with the selected modulation parameters. Typically, themodulation parameters programmed into the neuromodulation device can beadjusted by manipulating controls on the external control device tomodify the electrical modulation energy delivered by the neuromodulationdevice system to the patient. Thus, in accordance with the modulationparameters programmed by the external control device, electrical pulsescan be delivered from the neuromodulation device to the electrode(s) tomodulate a volume of tissue in accordance with the set of modulationparameters and provide the desired efficacious therapy to the patient.The best modulation parameter set will typically be one that deliverselectrical energy to the volume of tissue that must be modulate in orderto provide the therapeutic benefit (e.g., treatment of pain), whileminimizing the volume of non-target tissue that is modulated.

However, the number of electrodes available combined with the ability togenerate a variety of complex electrical pulses, presents a hugeselection of modulation parameter sets to the clinician or patient. Forexample, if the neuromodulation system to be programmed has an array ofsixteen electrodes, millions of modulation parameter sets may beavailable for programming into the neuromodulation system. Today,neuromodulation system may have up to thirty-two electrodes, therebyexponentially increasing the number of modulation parameters setsavailable for programming.

To facilitate such selection, the clinician generally programs theneuromodulation device through a computerized programming system. Thisprogramming system can be a self-contained hardware/software system, orcan be defined predominantly by software running on a standard personalcomputer (PC). The PC or custom hardware may actively control thecharacteristics of the electrical pulses generated by theneuromodulation device to allow the optimum modulation parameters to bedetermined based on patient feedback or other means and to subsequentlyprogram the neuromodulation device with the optimum modulation parameterset or sets. The computerized programming system may be operated by aclinician attending the patient in several scenarios.

For example, in order to achieve an effective result from conventionalSCS, the lead or leads must be placed in a location, such that theelectrical modulation (and in this case, electrical modulation) willcause paresthesia. The paresthesia induced by the electrical modulationand perceived by the patient should be located in approximately the sameplace in the patient's body as the pain that is the target of treatment.If a lead is not correctly positioned, it is possible that the patientwill receive little or no benefit from an implanted SCS system. Thus,correct lead placement can mean the difference between effective andineffective pain therapy. When leads are implanted within the patient,the computerized programming system, in the context of an operating room(OR) mapping procedure, may be used to instruct the neuromodulationdevice to apply electrical modulation to test placement of the leadsand/or electrodes, thereby assuring that the leads and/or electrodes areimplanted in effective locations within the patient.

Once the leads are correctly positioned, a fitting procedure, which maybe referred to as a navigation session, may be performed using thecomputerized programming system to program the external control device,and if applicable the neuromodulation device, with a set of modulationparameters that best addresses the painful site. Thus, the navigationsession may be used to pinpoint the volume of activation (VOA) or areascorrelating to the pain. Such programming ability is particularlyadvantageous for targeting the tissue during implantation, or afterimplantation should the leads gradually or unexpectedly move that wouldotherwise relocate the modulation energy away from the target site. Byreprogramming the neuromodulation device (typically by independentlyvarying the modulation energy on the electrodes), the volume ofactivation (VOA) can often be moved back to the effective pain sitewithout having to re-operate on the patient in order to reposition thelead and its electrode array. When adjusting the volume of activation(VOA) relative to the tissue, it is desirable to make small changes inthe proportions of current, so that changes in the spatial recruitmentof nerve fibers will be perceived by the patient as being smooth andcontinuous and to have incremental targeting capability.

Although alternative or artifactual sensations are usually toleratedrelative to the sensation of pain, patients sometimes report thesesensations to be uncomfortable, and therefore, they can be considered anadverse side-effect to neuromodulation therapy in some cases. Becausethe perception of paresthesia has been used as an indicator that theapplied electrical energy is, in fact, alleviating the pain experiencedby the patient, the amplitude of the applied electrical energy isgenerally adjusted to a level that causes the perception of paresthesia.It has been shown, however, that the delivery of sub-thresholdelectrical energy (e.g., high-rate pulsed electrical energy and/or lowpulse width electrical energy) can be effective in providingneuromodulation therapy for chronic pain without causing paresthesia.

However, because there is a lack of paresthesia that may otherwiseindicate that the activated electrodes are properly located relative tothe targeted tissue site, it is difficult to immediately determine ifthe delivered sub-threshold neuromodulation therapy is optimized interms of both providing efficacious therapy and minimizing energyconsumption. Furthermore, if the implanted neuromodulation lead(s)migrate relative to the target tissue site to be modulated, it ispossible that the sub-threshold neuromodulation may fall outside of theeffective therapeutic range (either below the therapeutic range if thecoupling efficiency between the neuromodulation lead(s) and targettissue site decreases, resulting in a lack of efficacious therapy, orabove the therapeutic range if the coupling efficiency between theneuromodulation lead(s) and the target tissue site increases, resultingin the perception of paresthesia or inefficient energy consumption).Similarly, a change in the patient's physical activity and/or posturemay also cause the neuromodulation lead(s) to migrate relative to thetarget tissue, and/or alternatively impede optimal treatment contact tothe target tissue, consequently rendering the sub-thresholdneuromodulation therapy inefficacious.

There, thus, remains a need to provide a neuromodulation system that iscapable of compensating for the migration of neuromodulation lead(s)and/or a change in physical activity and/or posture during sub-thresholdneuromodulation therapy.

SUMMARY OF THE INVENTION

In accordance with a first aspect of the present inventions, a method ofproviding therapy to a patient is provided. The method comprisesdelivering electrical modulation energy to a target tissue site of thepatient at a programmed intensity value (e.g., an amplitude value or apulse width value), thereby providing therapy to the patient without theperception of paresthesia, delivering, in response to an event,electrical modulation energy at a series of incrementally increasingintensity values relative to the programmed intensity value, sensing atleast one evoked compound action potential (eCAP) in a population ofneurons at the target tissue site of the patient in response to thedelivery of the electrical modulation energy at the series ofincrementally increasing intensity values of the electrical modulationenergy, selecting one of the series of incrementally increased intensityvalues based on the at least one sensed eCAP, automatically computing adecreased intensity value as a function of the selected intensity valueand delivering electrical modulation energy to the target tissue site ofthe patient at the computed intensity value.

In one method, the selected intensity value may correspond to theintensity value of the delivered electrical modulation energy inresponse to which a first one of the at least eCAP is sensed.

The method may also include comparing a characteristic of each of the atleast one sensed eCAP to a corresponding characteristic of a referenceeCAP that is indicative of a perception threshold and selecting one ofthe series of incrementally increased intensity values based on thecomparison. The characteristic of the each sensed eCAP may be at leastone a peak delay, width, amplitude and waveform morphology.

When the sensed eCAP comprises two or more eCAPs respectively sensed inresponse to the delivery of the electrical modulation energy at two ormore of the intensity values, the method may also include obtaining thecharacteristic from a stored reference eCAP, determining one of the twoor more sensed eCAPs having the characteristic that best matches thecharacteristic of the reference eCAP.

The characteristic of the reference eCAP may be a stored thresholdvalue. When the at least one sensed eCAP comprises one or more eCAPsrespectively sensed in response to the delivery of the electricalmodulation energy at each of two or more of the intensity values, themethod may also comprise determining a function of the one or moresensed eCAPs having the characteristic that equals or exceeds thethreshold value.

The method may also include storing a list of reference eCAPscharacteristics, each of which is indicative of a perception thresholdwhen the patient is engaged in a particular physical activity and/orposture, identifying a physical activity and/or posture in which thepatient is currently engaged, and selecting, from the list of referenceeCAP characteristics, the reference eCAP characteristic corresponding tothe identified physical activity and/or posture, and comparing thecharacteristic of each of the at least one sensed eCAP to the selectedreference eCAP.

The event may be an identified physical activity and/or posture, auser-initiated signal, a signal indicating migration of an electrodefrom which the electrical modulation energy is delivered, and apredetermined periodically recurring signal. The user-initiated signalmay be generated by an external control device in some methods.

The computed function may be percentage of the selected intensity value.The percentage may be in the range of 10%-90%, 40%-60%, or 30%-70%. Inanother method, the computed function may be a difference between theselected intensity value and a constant.

In accordance with a second aspect of the present inventions, aneuromodulation system for use with a patient is provided. Theneuromodulation system comprises a plurality of electrical terminalsconfigured to be respectively coupled to a plurality of electrodesimplanted within a target tissue site, modulation output circuitrycoupled to the plurality of electrical terminals to deliver electricalmodulation energy to the target tissue site of the patient at aprogrammed intensity value, thereby providing therapy to the patientwithout the perception of paresthesia, monitoring circuitry coupled tothe plurality of electrical terminals, control/processing circuitryconfigured to direct, in response to an event, the modulation outputcircuitry to deliver electrical modulation energy at a series ofincrementally increasing intensity values relative to the programmedintensity value, prompt the modulation output circuitry to evoke atleast one compound action potential (CAP) in a population of neurons inthe target tissue site of the patient in response to the delivery of theelectrical modulation energy at the series of incrementally increasedintensity values, prompt the monitoring circuitry to sense the at leastone evoked CAP (eCAP), select one of the series of incrementallyincreased intensity values based on the at least one sensed eCAP,automatically compute a decreased value as a function of the selectedintensity value, and direct the modulation output circuitry to deliverelectrical modulation energy to the target tissue site of the patient atthe computed intensity value.

In one embodiment, the selected intensity value corresponds to theintensity value of the delivered electrical modulation energy inresponse to which a first one of the at least one eCAP is sensed.

In another embodiment, the neuromodulation system further comprises amemory configured to store at least one characteristic of a referenceeCAP indicative of a perception threshold. The controller/processingcircuitry may be further configured to compare a characteristic of eachof the at least one sensed eCAP to a corresponding characteristic of areference eCAP, and select one of the series of incrementally increasedintensity values based on the comparison. The characteristic of the eachsensed eCAP may be at least one a peak delay, width, amplitude andwaveform morphology.

When the sensed eCAP comprises two or more eCAPs respectively sensed inresponse to the delivery of the electrical modulation energy at two ormore of the intensity values, the control/processing circuitry may befurther configured to obtain the characteristic from a stored referenceeCAP, determine one of the two or more sensed eCAPs having thecharacteristic that best matches the characteristic of the referenceeCAP, and select the intensity value of the delivered electricalmodulation energy in response to which the determined eCAP is sensed.

When the at least one sensed eCAP comprises one or more eCAPsrespectively sensed in response to the delivery of the electricalmodulation energy at each of two or more of the intensity values, thecontrol/processing circuitry may be further configured to determine afunction of the one or more sensed eCAPs having the characteristic thatequals or exceeds the threshold value and select the intensity value ofthe delivered electrical modulation energy in response to which thedetermined one or more eCAPs is sensed.

In another embodiment, the memory may be further configured to store alist of reference eCAP characteristics, each of which is indicative of aperception threshold when the patient is engaged in a particularphysical activity and/or posture. The control/processing circuitry maybe further configured to identify a physical activity and/or posture inwhich the patient is currently engaged, and select, from the list ofreference eCAP characteristics, the reference eCAP characteristiccorresponding to the identified physical activity and/or posture, andcompare the characteristic of each of the at least one sensed eCAP tothe selected reference eCAP.

Other and further aspects and features of the invention will be evidentfrom reading the following detailed description of the preferredembodiments, which are intended to illustrate, not limit, the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate the design and utility of preferred embodimentsof the present invention, in which similar elements are referred to bycommon reference numerals. In order to better appreciate how theabove-recited and other advantages and objects of the present inventionsare obtained, a more particular description of the present inventionsbriefly described above will be rendered by reference to specificembodiments thereof, which are illustrated in the accompanying drawings.Understanding that these drawings depict only typical embodiments of theinvention and are not therefore to be considered limiting of its scope,the invention will be described and explained with additionalspecificity and detail through the use of the accompanying drawings inwhich:

FIG. 1 is a plan view of a Spinal Cord Modulation (SCM) systemconstructed in accordance with one embodiment of the present inventions;

FIG. 2 is a profile view of an implantable pulse generator (IPG) used inthe SCM system of FIG. 1;

FIG. 3 is a plan view of the SCM system of FIG. 1 in use with a patient;

FIG. 4 is a block diagram of the internal components of the IPG of FIG.2; and

FIG. 5 is a flow diagram illustrating one method performed by the IPG ofFIG. 2 to compute a suitable amplitude for sub-threshold modulationtherapy.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The description that follows relates to a spinal cord modulation (SCM)system. However, it is to be understood that the while the inventionlends itself well to applications in SCM, the invention, in its broadestaspects, may not be so limited. Rather, the invention may be used withany type of implantable electrical circuitry used to stimulate tissue.For example, the present invention may be used as part of a pacemaker, adefibrillator, a cochlear stimulator, a retinal stimulator, a stimulatorconfigured to produce coordinated limb movement, a cortical stimulator,a deep brain stimulator, peripheral nerve stimulator, microstimulator,or in any other neural stimulator configured to treat urinaryincontinence, sleep apnea, shoulder sublaxation, headache, etc.

Turning first to FIG. 1, an exemplary SCM system 10 generally includes aplurality (in this case, two) of implantable neuromodulation leads 12,an implantable pulse generator (IPG) 14, an external remote controllerRC 16, a clinician's programmer (CP) 18, an external trial modulator(ETM) 20, and an external charger 22.

The IPG 14 is physically connected via one or more percutaneous leadextensions 24 to the neuromodulation leads 12, which carry a pluralityof electrodes 26 arranged in an array. In the illustrated embodiment,the neuromodulation leads 12 are percutaneous leads, and to this end,the electrodes 26 are arranged in-line along the neuromodulation leads12. The number of neuromodulation leads 12 illustrated is two, althoughany suitable number of neuromodulation leads 12 can be provided,including only one. Alternatively, a surgical paddle lead in can be usedin place of one or more of the percutaneous leads. As will be describedin further detail below, the IPG 14 includes pulse generation circuitrythat delivers electrical modulation energy in the form of a pulsedelectrical waveform (i.e., a temporal series of electrical pulses) tothe electrode array 26 in accordance with a set of modulationparameters.

The ETM 20 may also be physically connected via the percutaneous leadextensions 28 and external cable 30 to the neuromodulation leads 12. TheETM 20, which has similar pulse generation circuitry as the IPG 14, alsodelivers electrical modulation energy in the form of a pulse electricalwaveform to the electrode array 26 accordance with a set of modulationparameters. The major difference between the ETM 20 and the IPG 14 isthat the ETM 20 is a non-implantable device that is used on a trialbasis after the neuromodulation leads 12 have been implanted and priorto implantation of the IPG 14, to test the responsiveness of themodulation that is to be provided. Thus, any functions described hereinwith respect to the IPG 14 can likewise be performed with respect to theETM 20. For purposes of brevity, the details of the ETM 20 will not bedescribed herein.

The RC 16 may be used to telemetrically control the ETM 20 via abi-directional RF communications link 32. Once the IPG 14 andneuromodulation leads 12 are implanted, the RC 16 may be used totelemetrically control the IPG 14 via a bi-directional RF communicationslink 34. Such control allows the IPG 14 to be turned on or off and to beprogrammed with different modulation parameter sets. The IPG 14 may alsobe operated to modify the programmed modulation parameters to activelycontrol the characteristics of the electrical modulation energy outputby the IPG 14. As will be described in further detail below, the CP 18provides clinician detailed modulation parameters for programming theIPG 14 and ETM 20 in the operating room and in follow-up sessions.

The CP 18 may perform this function by indirectly communicating with theIPG 14 or ETM 20, through the RC 16, via an IR communications link 36.Alternatively, the CP 18 may directly communicate with the IPG 14 or ETM20 via an RF communications link (not shown). The clinician detailedmodulation parameters provided by the CP 18 are also used to program theRC 16, so that the modulation parameters can be subsequently modified byoperation of the RC 16 in a stand-alone mode (i.e., without theassistance of the CP 18).

The external charger 22 is a portable device used to transcutaneouslycharge the IPG 14 via an inductive link 38. Once the IPG 14 has beenprogrammed, and its power source has been charged by the externalcharger 22 or otherwise replenished, the IPG 14 may function asprogrammed without the RC 16 or CP 18 being present.

For purposes of brevity, the details of the RC 16, CP 18, ETM 20, andexternal charger 22 will not be described herein. Details of exemplaryembodiments of these devices are disclosed in U.S. Pat. No. 6,895,280,which is expressly incorporated herein by reference.

Referring now to FIG. 2, the external features of exemplaryneuromodulation leads 12 and the IPG 14 will be briefly described. Oneof the neuromodulation leads 12(1) has eight electrodes 26 (labeledE1-E8), and the other neuromodulation lead 12(2) has eight electrodes 26(labeled E9-E16). Of course, the number and shape of the leads and theelectrodes may vary based on the intended application of theneuromodulation system. Further details describing the construction andmethod of manufacturing percutaneous neuromodulation leads are disclosedin U.S. Pat. No. 8,019,439, entitled “Lead Assembly and Method of MakingSame,” and U.S. Pat. No. 7,650,184, entitled “Cylindrical Multi-ContactElectrode Lead for Neural Stimulation and Method of Making Same,” whichare expressly incorporated herein by reference. In some embodiments, asurgical paddle lead can be utilized, the details of which are disclosedin U.S. Patent Publication. No. 2007/0150036 A1, entitled “StimulatorLeads and Methods for Lead Fabrication and 2012/0059446 A1 entitledCollapsible/Expandable Tubular Electrode Leads,” which is expresslyincorporated herein by reference.

The IPG 14 comprises an outer case 40 for housing the electronic andother components (described in further detail below), and a connector 42to which the proximal ends of the neuromodulation leads 12 mate in amanner that electrically couples the electrodes 26 to the electronicswithin the outer case 40. The outer case 40 is composed of anelectrically conductive, biocompatible material, such as titanium, andforms a hermetically sealed compartment wherein the internal electronicsare protected from the body tissue and fluids. In some cases, the outercase 40 may serve as an electrode.

The IPG 14 includes a pulse generation circuitry that provideselectrical modulation energy to the electrodes 26 in accordance with aset of modulation parameters. Such parameters may include electrodecombinations, which define the electrodes that are activated as anodes(positive), cathodes (negative), and turned off (zero). The modulationparameters may further include pulse amplitude (measured in milliamps orvolts depending on whether the IPG 14 supplies constant current orconstant voltage to the electrodes), pulse width (measured inmicroseconds), pulse rate (measured in pulses per second), duty cycle(pulse width divided by cycle duration), burst rate (measured as themodulation energy on duration X and modulation energy off duration Y),and pulse shape.

With respect to the pulse patterns provided during operation of thesystem 10, electrodes that are selected to transmit or receiveelectrical energy are referred to herein as “activated,” whileelectrodes that are not selected to transmit or receive electricalenergy are referred to herein as “non-activated.” Electrical energydelivery will occur between two (or more) electrodes, one of which maybe the IPG outer case 40. Electrical energy may be transmitted to thetissue in a monopolar or multipolar (for example, bipolar, tripolar andsimilar configurations) fashion or by any other means available.

The IPG 14 may be operated in either a super-threshold delivery mode ora sub-threshold delivery mode. While in the super-threshold deliverymode, the IPG 14 is configured for delivering electrical modulationenergy that provides super-threshold therapy to the patient (in thiscase, causes the patient to perceive paresthesia). For example, anexemplary super-threshold pulse train may be delivered at a relativelyhigh pulse amplitude (e.g., 5 ma), a relatively low pulse rate (e.g.,less than 1500 Hz, preferably less than 500 Hz), and a relatively highpulse width (e.g., greater than 100 μs, preferably greater than 200 μs).

While in the sub-threshold delivery mode, the IPG 14 is configured fordelivering electrical modulation energy that provides sub-thresholdtherapy to the patient (in this case, does not cause the patient toperceive paresthesia). For example, an exemplary sub-threshold pulsetrain may be delivered at a relatively low pulse amplitude (e.g., 2.5ma), a relatively high pulse rate (e.g., greater than 1500 Hz,preferably greater than 2500 Hz), and a relatively low pulse width(e.g., less than 100 Cps, preferably less than 50 μs).

As shown in FIG. 3, the neuromodulation leads 12 are implanted withinthe spinal column 46 of a patient 48. The preferred placement of theneuromodulation leads 12 is adjacent, i.e., resting near, or upon thedura, adjacent to the spinal cord area to be stimulated. Theneuromodulation leads 12 will be located in a vertebral position thatdepends upon the location and distribution of the chronic pain. Forexample, if the chronic pain is in the lower back or legs, theneuromodulation leads 12 may be located in the mid- to low-thoracicregion (e.g., at the T9-12 vertebral levels). Due to the lack of spacenear the location where the neuromodulation leads 12 exits the spinalcolumn 46, the IPG 14 is generally implanted in a surgically-made pocketeither in the abdomen or above the buttocks. The IPG 14 may, of course,also be implanted in other locations of the patient's body. The leadextensions 24 facilitate locating the IPG 14 away from the exit point ofthe electrode leads 12. As there shown, the CP 18 communicates with theIPG 14 via the RC 16.

More significant to the present inventions, because sub-thresholdtherapy does not produce paresthesia, it is important to continuouslymonitor the sub-threshold modulation energy to ensure that the patientis receiving optimal treatment. To this end, the IPG 14 is configured toautomatically initiate calibration of sub-threshold therapy that mayhave fallen outside of the therapeutic range. The goal of thecalibration process is to determine a perception threshold, and thencompute a decreased intensity value as a function of the perceptionthreshold to be used in sub-threshold modulation therapy.

In the illustrated embodiment, initiation of the calibration process maybe triggered by a particular event, such as, e.g., a user actuation of acontrol element located on the RC 16 or CP, a sensor signal indicatingthat one or more of the neuromodulation leads 12 has migrated relativeto a target site in the patient, a sensor signal indicating that thepatient's physical activity and/or posture has changed relative to aprevious physical activity and/or posture, or a periodically recurringsignal generated in response to an elapsed time, a time of day, day ofthe week, etc.

Once the sub-threshold calibration is initiated, the SCM system 10delivers the modulation output energy to the electrodes 26 atincrementally increasing intensity values, such as amplitude values(e.g., amplitude at a 0.1 mA step size). Preferably, if the amplitudevalues are incrementally increased, the other modulation parameters,such as the electrode combination, pulse rate, and pulse width are notaltered during the incremental increase of the amplitude. Thus, the onlymodulation parameter of the sub-threshold modulation program that isaltered is the pulse amplitude. In the instance in which the intensityvalue is pulse width (e.g., at a 10 μs step size), the only modulationparameter of the sub-threshold modulation program that is altered inpulse width.

In response to the delivered electrical modulation energy at theincrementally increasing intensity values, at least one compound actionpotential (CAP) is evoked by the modulation of neural tissue at thetarget tissue site. An evoked CAP (eCAP) is the simultaneous evoking ofaction potentials traveling down a population of neurons. Thus, thetotal magnitude of the eCAP is proportional to the number of neuronsthat are carrying action potentials, and therefore, may function as aclinical measurement as to the intensity level (i.e., strength of theconveyed electrical modulation energy), which is both the dose oftherapy that is used to decrease the pain in the patient, and thephysiological signal that causes the patient to perceive eithercomfortable paresthesia, painful overstimulation, or lack ofstimulation. Significantly, the eCAP(s) (which in some cases, may onlybe one eCAP, and in other cases may be several eCAPs) are used asindicators of the perception threshold of the patient. To this end, theSCM system 10 senses and measures these eCAP(s), the characteristics ofwhich may be used to ultimately determine a suitable intensity forsub-threshold modulation therapy, as will be described in further detailbelow.

To determine the perception threshold, the SCM system 10 evaluates themeasured eCAP(s) and selects intensity value corresponding to at leastone of the measured eCAP(s) as the perception threshold.

In one embodiment, the SCM system 10 may automatically select theamplitude value at which a first eCAP is sensed as the perceptionthreshold. For example, when the amplitude of the delivered electricalmodulation energy is incrementally increased, the first eCAP may besensed at 5.1 mA. Thus, the SCM system 10 may select the amplitude valuecorresponding to 5.1 mA as the perception threshold.

Alternatively, the SCM system 10 may automatically select the amplitudevalue based on a comparison between the measured eCAPs and a referenceeCAP indicative of the perception threshold. The reference eCAP, whichmay be determined empirically, captures the characteristics of an eCAPat the amplitude of the delivered electrical modulation energy at whichthe patient felt paresthesia (the perception threshold). This referenceeCAP (or a characteristic or characteristics of the reference eCAP) maythen be used to compare the eCAP(s) (or characteristics of the eCAPs)measured in response to the delivery of the electrical modulation energyduring the calibration process. The characteristics of the eCAP mayinclude, e.g., amplitude, peak delay, width, as well as waveformmorphology.

For example, in one technique, the SCM system 10 may compare a waveformmorphology of the measured eCAP to the waveform morphology of thereference eCAP to select the eCAP whose waveform morphology most closelyresembles that of the reference eCAP. Thus, the amplitude of thedelivered energy that resulted in the eCAP that most closely resemblesthe reference eCAP is determined to be the perception threshold.

In another technique, the SCM system 10 may store a particularcharacteristic of the reference eCAP as a threshold value to be used indetermining the perception threshold. In this case, the SCM system 10may compare a value of a selected characteristic of the measured eCAP tothe stored threshold value. In one example, the threshold value maysimply be the amplitude of the reference eCAP. In such a case, when theamplitude of a measured eCAP is equal to or greater than the thresholdvalue, the amplitude of the delivered energy that resulted in thatmeasured eCAP is determined to be the perception threshold. In anotherexample, the threshold value may be the peak delay of the referenceeCAP, such that when the peak delay of a measured eCAP is equal to orgreater than the threshold value, the amplitude of the delivered energythat resulted in that measured eCAP is determined to be the perceptionthreshold. In yet another example, the threshold value may be width ofthe reference eCAP, such that when the width of a measured eCAP is equalto or greater than the threshold value, the amplitude of the deliveredenergy that resulted in that measured eCAP is determined to be theperception threshold.

Although the previous examples have been focused on comparing acharacteristic of a single eCAP to the reference eCAP, it should beappreciated that a function of characteristic(s) of multiple eCAPmeasurements may be compared to the reference eCAP. That is, becausemultiple eCAPs may be measured in response to the corresponding pulsesin the electrical pulse train delivered at a specific amplitude value, afunction (e.g., an average) of a characteristic of these eCAPs may becompared to the reference eCAP. This can be particularly useful inincreasing the signal-to-noise ratio. For example, assume that anelectrical pulse train comprises ten pulses in response to which teneCAP measurements are respectively made. When the amplitude of theelectrical pulse train is high enough, or close to that of theperception threshold, ten eCAPs may be measured in response to the tenpulses. Any one of these measured eCAPs will thus be truly indicative ofthe perception threshold. When the amplitude of the electrical pulsetrain is at a lower level, however, only one CAP may be evoked inresponse to the ten pulses and the other nine of the eCAP measurementsmay be zero. This one measured eCAP will thus not be indicative of theperception threshold.

To avoid such anomalies that may be caused by noise and/or systemerrors, an average of all the eCAP measurements at a particularamplitude value may render more accurate results than using individualeCAP measurements. It should be appreciated that the signal-to-noiseratio is reduced when a higher number of eCAP measured are used forcomparison, bringing the average of the eCAP measurements closer to thetrue indication of whether or not the perception threshold has beenreached. Thus, to increase the signal-to-noise ratio, the average of theeCAP measurements for each amplitude value of the delivered electricalpulse train may be compared to the reference eCAP. For example, if theaverage of all the eCAP measurements made in response to an electricalpulse train of a particular amplitude value equal or exceed thethreshold value, that amplitude value is determined to be the perceptionthreshold.

Although in the previous embodiments, only one reference eCAP isdescribed as being stored, multiple reference eCAPs from which onereference eCAP can be selected for comparison can be stored. Forexample, in one embodiment, the SCM system 10 may store a list ofreference eCAPs associated with a set of patient activities and/orpostures. The perception threshold and corresponding reference eCAP maybe different when the patient is walking as compared to when the patientis lying down, or sitting. These reference eCAPs, which are indicativeof perception thresholds when the patient is engaged in a particularactivity and/or posture, may be determined empirically and recorded. Forexample, each physical activity and/or posture may be characterized inthe laboratory for each individual patient to generate a personalizedlook-up table that correlates the physical activity and/or posture witha reference eCAP. The SCM system 10 is configured to identify thephysical activity and/or posture of the patient, as will be describedbelow, and select the appropriate reference eCAP for comparison with themeasured eCAP(s).

There may be many ways to identify the physical activity and/or postureof the patient. In one technique, the patient's physical activity and/orposture may be tracked and identified by measuring electrical parameterdata (i.e., interelectrode impedance and/or measured field potentials)and performing time-varying analysis on the measured electricalparameter data, as disclosed in U.S. Patent Publication. No.2008/0188909 A1, entitled “Neurostimulation system and method formeasuring patient activity,” which is expressly incorporated herein byreference. In another technique, the patient's physical activity and/orposture may be tracked and identified using an orientation sensitivedevice that is implanted in the IPG 14, as described in U.S. patentapplication Ser. No. 13/446,191, entitled “Sensing Device For IndicatingPosture of a Patient Implanted With a Neurostimulation Device,” which isexpressly incorporated herein by reference. In still another technique,the patient's physical activity and/or posture may be tracked andidentified by measuring characteristic impedance waveform morphologies,as described in U.S. Pat. No. 7,317,948, which is expressly incorporatedherein by reference.

It should be appreciated that the physical activity and/or posture ofthe patient may be identified regardless of the nature of the event thattriggers the calibration process. Thus, the calibration process may beinitiated by an event independent from the identification of thephysical activity and/or posture, in which case, the physical activityand/or posture is identified only to determine the reference eCAP forcomparison with the measured eCAPs. However, the event itself may beidentification of a triggering physical activity and/or posture, inwhich case, the calibration process is initiated by it in addition tohelping determine the reference eCAP. For example, the SCM system 10might detect that the patient is engaged in a triggering physicalactivity (e.g., running) and initiate the calibration process. In thiscase, the SCM system 10 is similarly configured to select the referenceeCAP associated with the identified triggering physical activity and/orposture and compare the selected reference eCAP with the measuredeCAP(s) to determine the perception threshold. Constantly calibratingthe SCM system 10 whenever the patient changes his posture or physicalactivity may prove to be rather inefficient. Accordingly, the SCM system10 may be provided with a predetermined list of triggering physicalactivities, such that the SCM system 10 only initiates the calibrationprocess when a triggering physical activity and/or posture isidentified. For example, only physical strenuous activities likerunning, lifting weights, etc., may trigger calibration.

Once the perception threshold has been determined, the SCM system 10automatically computes a decreased amplitude for sub-thresholdmodulation as a function of the perception threshold. The function ofthe selected amplitude value is designed to ensure that the modulationenergy subsequently delivered to the patient at the computed amplitudevalue falls within the sub-threshold therapy range. For example, thecomputed function may be a percentage (preferably in the range of30%-70%, and more preferably in the range of 40%-60%) of the lastincrementally increased amplitude value. As another example, thecomputed function may be a difference between the last incrementallyincreased amplitude value and a constant (e.g., 1 mA). The SCM system 10is also configured for modifying the sub-threshold modulation programstored in the IPG 14, such that the modulation energy is delivered tothe electrodes 26 in accordance with the modified modulation program atthe computed amplitude value.

Turning next to FIG. 4, one exemplary embodiment of the IPG 14 will nowbe described. The IPG 14 includes modulation output circuitry 50configured for generating electrical modulation energy in accordancewith an electrical pulse train having a programmed pulse amplitude,pulse rate, pulse width, duty cycle, burst rate, and shape under controlof control logic 52 over data bus 54. The pulse rate and the duration ofstimulation may be controlled by analog circuitry, or digital timerlogic circuitry 56 controlling the analog circuitry, and which may havea suitable resolution, e.g., 10 μs. The modulation energy generated bythe modulation output circuitry 50 is output via capacitors C1-C16 toelectrical terminals 58 respectively corresponding to electrodes E1-E16.

The modulation output circuitry 50 may either include independentlycontrolled current sources for providing modulation pulses of aspecified and known amperage to or from the electrical terminals 58, orindependently controlled voltage sources for providing modulation pulsesof a specified and known voltage at the electrical terminals 58 or tomultiplexed current or voltage sources that are then connected to theelectrical terminals 58. The operation of this modulation outputcircuitry 50, including alternative embodiments of suitable outputcircuitry for performing the same function of generating modulationpulses of a prescribed amplitude and width, is described more fully inU.S. Pat. Nos. 6,516,227 and 6,993,384, which are expressly incorporatedherein by reference. Thus, it can be appreciated that the modulationoutput circuitry 50 is capable of delivering electrical energy to theelectrodes 26 via the electrical terminals 58 at a series ofincrementally increasing amplitude values when the calibration processis initiated, and for the purpose of evoking CAPs in the neural tissuein response to the series of incrementally increasing amplitude valuesand/or for delivering sub-threshold modulation therapy based on theperception threshold determined through the process of calibration.

The modulation output circuitry 50 may either include independentlycontrolled current sources for providing stimulation pulses of aspecified and known amperage to or from the electrical terminals 58, orindependently controlled voltage sources for providing stimulationpulses of a specified and known voltage at the electrical terminals 58or to multiplexed current or voltage sources that are then connected tothe electrical terminals 58. The operation of this modulation outputcircuitry 50, including alternative embodiments of suitable outputcircuitry for performing the same function of generating stimulationpulses of a prescribed amplitude and width, is described more fully inU.S. Pat. Nos. 6,516,227 and 6,993,384, which are expressly incorporatedherein by reference.

Thus, it can be appreciated that the modulation output circuitry 50 iscapable of delivering electrical energy to the electrodes 26 via theelectrical terminals 58 for the purpose of providing therapy to thepatient and/or evoking CAPs in the neural tissue during the calibrationprocess described above.

The IPG 14 also includes monitoring circuitry 60 for monitoring thestatus of various nodes or other points 62 throughout the IPG 14, e.g.,power supply voltages, temperature, battery voltage, and the like.Notably, the electrodes 26 fit snugly within the epidural space of thespinal column, and because the tissue is conductive, electricalmeasurements can be taken from the electrodes 26 in order to determinethe coupling efficiency between the respective electrode 26 and thetissue and/or to facilitate fault detection with respect to theconnection between the electrodes 26 and the modulation output circuitry60 of the IPG 14.

More significant to the present inventions, the monitoring circuitry 60is configured to measure characteristic(s) of the CAPs evoked inresponse to the stimulation of neural tissue via the modulation outputcircuitry 50 during the calibration process. The evoked potentialmeasurement technique may be performed by generating an electrical fieldat one of the electrodes 26, which is strong enough to depolarize theneurons adjacent the stimulating electrode beyond a threshold level,thereby inducing the firing of an eCAP that propagates along the neuralfibers. Such stimulation is preferably supra-threshold, but notuncomfortable. A suitable stimulation pulse for this purpose is, forexample, 4 mA for 200 μs. While a selected one of the electrodes 26 isactivated to generate the electrical field, a selected one or ones ofthe electrodes 26 (different from the activated electrode) is operatedto record a measurable deviation in the voltage caused by the evokedpotential due to the stimulation pulse at the stimulating electrode. Tothe extent that other physiological information is acquired for thepurpose of triggering the modulation parameter adjustment process, themonitoring circuitry 60 may be coupled to various sensors. If thephysiological measurements are electrical, the sensors may be one ormore of the electrodes 26. For other types of non-electricalphysiological information, however, separate sensors may be used forappropriate measurements.

The IPG 14 further includes a control/processing circuitry in the formof a microcontroller (μC) 64 (or a processor) that controls the controllogic 52 over data bus 66, and obtains status data from the monitoringcircuitry 60 via data bus 68. The IPG 14 additionally controls the timerlogic 56. The IPG 14 further includes memory 70 and oscillator and clockcircuit 72 coupled to the microcontroller 64.

Further, the microcontroller 64 generates the necessary control andstatus signals, which allow the microcontroller 64 to control theoperation of the IPG 14 in accordance with a selected operating programand modulation parameters. In controlling the operation of the IPG 14,the microcontroller 64 is able to individually generate electricalenergy at the electrodes 26 using the modulation output circuitry 50, incombination with the control logic 52 and timer logic 56, therebyallowing each electrode 26 to be paired or grouped with other electrodes26, including the monopolar case electrode, to control the polarity,pulse amplitude, pulse rate, pulse width, and pulse duty cycle throughwhich the electrical energy is provided. Further, the microcontroller 64initiates the calibration process in response to the event.

The microcontroller 64 is also configured for initiating and performingthe calibration process, including directing the modulation outputcircuitry 50 to deliver the electrical energy at increasing amplitudelevels, directing the monitoring circuitry 60 to sense any eCAPs inresponse to the delivered electrical energy, determining the perceptionthreshold of the patient in response to the sensing of the eCAPs, andcomputing a decreased amplitude suitable for sub-threshold modulationtherapy based on the perception threshold.

The memory 70 may store various data (e.g. modulation parameters,reference eCAPs, threshold values, etc.) and a series of instructions tobe executed by the microcontroller 64. The microcontroller 64, incombination with the memory 70 and oscillator and clock circuit 72, thusinclude a microprocessor system that carries out a program function inaccordance with a suitable program stored in the memory 70.Alternatively, for some applications, the control/processing functionsmay be carried out by a suitable state machine.

The IPG 14 further includes an alternating current (AC) receiving coil74 for receiving programming data (e.g., the operating program and/ormodulation parameters) from the RC 16 and/or CP 18 in an appropriatemodulated carrier signal, and charging and forward telemetry circuitry76 for demodulating the carrier signal it receives through the ACreceiving coil 74 to recover the programming data, which programmingdata is then stored within the memory 70, or within other memoryelements (not shown) distributed throughout the IPG 14.

The IPG 14 further includes a back telemetry circuitry 78 and analternating current (AC) transmission coil 80 for sending informationaldata sensed through the monitoring circuitry 60 to the RC 16 and/or CP18. The back telemetry features of the IPG 14 also allow its status tobe checked. For example, when the RC 16 and/or CP 18 initiates aprogramming session with the IPG 14, the capacity of the battery istelemetered, so that the RC 16 and/or CP 18 can calculate the estimatedtime to recharge. Any changes made to the current modulation parametersare confirmed through back telemetry, thereby assuring that such changeshave been correctly received and implemented within the implant system.Moreover, upon interrogation by the RC 16 and/or CP 18, all programmablesettings stored within the IPG 14 may be uploaded to the RC 16 and/or CP18.

Notably, if the RC 16, or alternatively the CP 18, is used to performthe automated modulation parameter adjustment technique, the measuredeCAPs can be transmitted from the IPG 14 to the RC 16 or CP 18 via theback telemetry circuitry 78 and coil 80. The RC 16 or the CP 18 mayperform the necessary routine to adjust the modulation parameters andtransmit the adjusted set of modulation parameters to the IPG 14 so thatthe IPG 14 can generate the electrical modulation energy in accordancewith the adjusted set of modulation parameters.

The IPG 14 further includes a rechargeable power source 82 and powercircuits 84 for providing the operating power to the IPG 14. Therechargeable power source 82 may, e.g., include a lithium-ion orlithium-ion polymer battery. The rechargeable battery 82 provides anunregulated voltage to the power circuits 84. The power circuits 84, inturn, generate the various voltages 86, some of which are regulated andsome of which are not, as needed by the various circuits located withinthe IPG 14. The rechargeable power source 82 is recharged usingrectified AC power (or DC power converted from AC power through othermeans, e.g., efficient AC-to-DC converter circuits, also known as“inverter circuits”) received by the AC receiving coil 74. To rechargethe power source 82, an external charger (not shown), which generatesthe AC magnetic field, is placed against, or otherwise adjacent, to thepatient's skin over the implanted IPG 14. The AC magnetic field emittedby the external charger induces AC currents in the AC receiving coil 74.The charging and forward telemetry circuitry 76 rectifies the AC currentto produce DC current, which is used to charge the power source 82.While the AC receiving coil 74 is described as being used for bothwirelessly receiving communications (e.g., programming and control data)and charging energy from the external device, it should be appreciatedthat the AC receiving coil 74 can be arranged as a dedicated chargingcoil, while another coil, such as coil 80, can be used forbi-directional telemetry.

Additional details concerning the above-described and other IPGs may befound in U.S. Pat. No. 6,516,227, U.S. Patent Publication No.2003/0139781, and U.S. Pat. No. 7,539,538, entitled “Low Power LossCurrent Digital-to-Analog Converter Used in an Implantable PulseGenerator,” which are expressly incorporated herein by reference. Itshould be noted that rather than the IPG 14, the system 10 mayalternatively utilize an implantable receiver-stimulator (not shown)connected to leads 12. In this case, the power source, e.g., a battery,for powering the implanted receiver, as well as control circuitry tocommand the receiver-stimulator, will be contained in an externalcontroller inductively coupled to the receiver-stimulator via anelectromagnetic link. Data/power signals are transcutaneously coupledfrom a cable-connected transmission coil placed over the implantedreceiver-stimulator. The implanted receiver-stimulator receives thesignal and generates the stimulation in accordance with the controlsignals.

Turning now to FIG. 5 an exemplary method 300 of using eCAPs toautomatically compute a decreased amplitude suitable for sub-thresholdmodulation therapy will be described. First, the SCM system 10 deliverselectrical modulation energy to a target tissue of the patient inaccordance with the sub-threshold modulation program stored within theSCM system 10, thereby providing therapy to the patient without theperception of paresthesia (step 302). Next, a calibration triggeringevent occurs (step 304). As previously discussed, such triggering eventcan be an identified triggering physical activity and/or posture, auser-initiated signal, a signal indicating electrode-migration or apredetermined periodically recurring signal. Next, the SCM system 10identifies the patient's physical activity and/or posture if it has notalready been identified as a triggering event (step 306). Based on thepatient/s physical activity and/or posture, the SCM system 10 selects,from the stored list of reference eCAPs, the reference eCAPcorresponding to the identified physical activity and/or posture (step308).

Next, the SCM system 10 delivers an electrical pulse train of aspecified amplitude (which may initially be the programmed amplitude atwhich the electrical pulse train was delivered to provide thesub-threshold therapy), in response to which eCAP measurements are madefor at least one pulse of the delivered electrical pulse train (step310). To increase the signal-to-noise ratio, an eCAP measurement may bemade after each pulse. Next, the SCM system 10 compares the eCAPmeasurement(s) to the selected reference eCAP corresponding to theidentified physical activity and/or posture (step 312). As previouslydiscussed, a characteristic (e.g., amplitude, peak delay, width,morphology) of an eCAP measurement or function of multiple eCAPmeasurements may be compared to the same characteristic of the referenceeCAP.

If the eCAP comparison reveals that the perception threshold of thepatient has not been reached (step 314), the SCM system 10 increases theamplitude of the delivered electrical energy by a step size (step 316),and returns to making eCAP measurement(s) in response to the deliveredelectrical energy at the increased amplitude (step 310). If the eCAPcomparison reveals that the perception threshold of the patient has beenreached (step 314), the SCM system 10 computes a decreased amplitudevalue as a function of the amplitude value indicative of the perceptionthreshold (step 318). As described above, such function can be, e.g., apercentage of the determined perception threshold or a differencebetween the determined perception threshold and a constant. The SCMsystem 10 then modifies the sub-threshold modulation program with thecomputed amplitude value (step 320) and returns to step 302 to directthe IPG 14 to deliver electrical modulation energy in accordance with amodified sub-threshold modulation program, thereby providing therapy tothe patient without the perception of paresthesia.

Thus, it can be appreciated that the sub-threshold calibration techniqueensures that any intended sub-threshold therapy remains within anefficacious and energy efficient therapeutic window that may otherwisefall outside of this window due to environmental changes, such as leadmigration or changes in patient's physical activity and/or posture.Although the sub-threshold calibration technique has been described withrespect to sub-threshold therapy designed to treat chronic pain, itshould be appreciated that this calibration technique can be utilized tocalibrate any sub-threshold therapy provided to treat a patient with anydisorder where the perception of paresthesia may be indicative ofefficacious treatment of the disorder. Furthermore, although thesub-threshold calibration technique has been described as beingperformed in the IPG 14, it should be appreciated that this techniquecould be performed in the CP 18, or even the RC 16.

It should also be appreciated that although the sub-thresholdcalibration technique has been described with the adjustment of theamplitude of the electrical modulation energy, it should be appreciatedthat other modulation parameters that affect the intensity of theelectrical modulation energy can be varied. For example, instead ofincrementally increasing amplitude values relative to a programmedamplitude value while maintaining the pulse width value and pulse ratevalue the same, and computing a decreased amplitude value as a functionof one of the increased amplitude values, pulse width values may beincrementally increased relative to a programmed pulse width value whilemaintaining the amplitude value and pulse rate value the same, andcomputing a decreased pulse width value as a function of one of theincreased pulse width value. The significance is that a parameter thatdirectly effects the intensity of the electrical modulation energy in acontrollable and predictable fashion is used to calibrate thesub-threshold therapy.

Although particular embodiments of the present inventions have beenshown and described, it will be understood that it is not intended tolimit the present inventions to the preferred embodiments, and it willbe obvious to those skilled in the art that various changes andmodifications may be made without departing from the spirit and scope ofthe present inventions. Thus, the present inventions are intended tocover alternatives, modifications, and equivalents, which may beincluded within the spirit and scope of the present inventions asdefined by the claims.

What is claimed is:
 1. A method, comprising: providing a sub-perceptiontherapy to a patient such that the patient does not perceivestimulation, wherein providing the sub-perception therapy includesinitiating the sub-perception therapy and delivering the sub-perceptiontherapy over a time period after the sub-perception therapy isinitiated, and wherein providing the sub-perception therapy includesdelivering electrical modulation energy to a target tissue site of thepatient at a programmed intensity value; automatically determiningoccurrences of an event during the time period after initiating thesub-perception therapy; automatically responding to each of theoccurrences of the event by performing an automatic calibration processfor the sub-perception therapy to update the programmed intensity valueaccounting for environmental changes during the time period afterinitiating the sub-perception therapy, wherein the automatic calibrationprocess that is automatically performed in response to each of theoccurrences of the event during the time period includes automaticallycalibrating the sub-perception therapy to a perception threshold inresponse to each of the occurrences of the event, wherein theautomatically calibrating the sub-perception therapy to the perceptionthreshold includes: automatically detecting the perception threshold bydelivering electrical modulation energy using a series of incrementallyincreasing intensity values relative to the programmed intensity valueto increase an intensity of the delivered electrical modulation energyto at least the perception threshold, and sensing at least one evokedcompound action potential (eCAP) indicative of the perception thresholdin a population of neurons at the target tissue site of the patient inresponse to the delivery of the electrical modulation energy at theseries of incrementally increasing intensity values; determining acorresponding intensity value from the series of incrementally increasedintensity values for the at least one sensed eCAP indicative of theperception threshold; determining a decreased intensity value based onthe corresponding intensity value; and updating the programmed intensityvalue for the electrical modulation energy using the decreased intensityvalue; continuing to deliver the sub-perception therapy during the timeperiod by delivering electrical modulation energy to the target tissuesite of the patient using the updated programmed intensity value.
 2. Themethod of claim 1, wherein the determining the decreased intensity valuebased on the corresponding intensity value includes determining apercentage of the corresponding intensity value.
 3. The method of claim1, wherein the programmed intensity value is a programmed amplitudevalue, and the incrementally increasing intensity values areincrementally increasing amplitude values.
 4. The method of claim 1,wherein the programmed intensity value is a programmed pulse widthvalue, and the incrementally increasing intensity values areincrementally increasing pulse width values.
 5. The method of claim 1,wherein the corresponding intensity value corresponds to the intensityvalue of the delivered electrical modulation energy in response to whicha first one of the at least one eCAP is sensed.
 6. The method of claim1, further comprising: comparing a characteristic of each of the atleast one sensed eCAP to a corresponding characteristic of a referenceeCAP indicative of a perception threshold; and determining one of thecorresponding intensity values based on the comparison.
 7. The method ofclaim 6, wherein the characteristic of the each sensed eCAP includesamplitude.
 8. The method of claim 6, wherein the characteristic of theeach sensed eCAP includes at least one of peak delay, width, or waveformmorphology.
 9. The method of claim 6, wherein the at least one sensedeCAP comprises two or more eCAPs respectively sensed in response to thedelivery of the electrical modulation energy at two or more of theintensity values, the method further comprising determining one of thetwo or more sensed eCAPs having the characteristic that best matches thecharacteristic of the reference eCAP, wherein selecting one of theseries of incrementally increased intensity values includes selectingthe intensity value that corresponds to the eCAP determined to bestmatch the reference eCAP.
 10. The method of claim 6, wherein thecharacteristic of the reference eCAP is a threshold value, the at leastone sensed eCAP comprises one or more eCAPs respectively sensed inresponse to the delivery of the electrical modulation energy at each oftwo or more of the intensity values, the method further comprisingdetermining a function of the one or more sensed eCAPs having thecharacteristic that equals or exceeds the threshold value.
 11. Themethod of claim 6, further comprising: identifying a physical activityand/or posture in which the patient is currently engaged; and selecting,from a list of reference eCAP characteristics indicative of a perceptionthreshold when the patient is engaged in a particular physical activityand/or posture, the reference eCAP characteristic corresponding to theidentified physical activity and/or posture.
 12. The method of claim 1,wherein the event is one of an identified physical activity and/orposture, a user-initiated signal, a signal indicating migration of anelectrode from which the electrical modulation energy is delivered, anda predetermined periodically recurring signal.
 13. The method of claim1, wherein the determined decreased intensity value is reduced by aconstant from the corresponding intensity value for the at least onesensed eCAP indicative of the perception threshold.
 14. The method ofclaim 1, wherein both the electrical modulation energy delivered at theprogrammed intensity and the electrical energy delivered at the seriesof incrementally increasing intensity values comprise electrical pulsetrains having a pulse intensity value.
 15. A non-transitorymachine-readable medium including instructions, which when executed by amachine, cause the machine to perform a method comprising: providing asub-perception therapy to a patient such that the patient does notperceive stimulation, wherein providing the sub-perception therapyincludes initiating the sub-perception therapy and delivering thesub-perception therapy over a time period after the sub-perceptiontherapy is initiated, and wherein providing the sub-perception therapyincludes delivering electrical modulation energy to a target tissue siteof the patient at a programmed intensity value; automaticallydetermining occurrences of an event during the time period afterinitiating the sub-perception therapy; automatically responding to eachof the occurrences of the event by performing an automatic calibrationprocess for the sub-perception therapy to update the programmedintensity value accounting for environmental changes during the timeperiod after initiating the sub-perception therapy, wherein theautomatic calibration process that is automatically performed inresponse to each of the occurrences of the event during the time periodincludes automatically calibrating the sub-perception therapy to aperception threshold in response to each of the occurrences of theevent, wherein the automatically calibrating the sub-perception therapyto the perception threshold includes: automatically detecting theperception threshold by delivering electrical modulation energy using aseries of incrementally increasing intensity values relative to theprogrammed intensity value to increase an intensity of the deliveredelectrical modulation energy to at least the perception threshold, andsensing at least one evoked compound action potential (eCAP) indicativeof the perception threshold in a population of neurons at the targettissue site of the patient in response to the delivery of the electricalmodulation energy at the series of incrementally increasing intensityvalues; determining a corresponding intensity value from the series ofincrementally increased intensity values for the at least one sensedeCAP indicative of the perception threshold; determining a decreasedintensity value based on the corresponding intensity value; and updatingthe programmed intensity value for the electrical modulation energyusing the decreased intensity value; continuing to deliver thesub-perception therapy during the time period by delivering electricalmodulation energy to the target tissue site of the patient using theupdated programmed intensity value.
 16. The non-transitorymachine-readable medium of claim 15, wherein the determining thedecreased intensity value based on the corresponding intensity valueincludes determining a percentage of the corresponding intensity value.17. The non-transitory machine-readable medium of claim 15, wherein themethod further comprises: comparing a characteristic of each of the atleast one sensed eCAP to a corresponding characteristic of a referenceeCAP indicative of a perception threshold; and determining one of thecorresponding intensity values based on the comparison.
 18. Thenon-transitory machine-readable medium of claim 17, wherein thecharacteristic of the each sensed eCAP includes at least one ofamplitude, peak delay, width, or waveform morphology.
 19. Aneurostimulation system, comprising: a neurostimulator configured toprovide a sub-perception therapy to a patient such that the patient doesnot perceive stimulation, wherein the sub-perception therapy is providedby initiating the sub-perception therapy and delivering thesub-perception therapy over a time period after the sub-perceptiontherapy is initiated, and wherein the sub-perception therapy is providedby delivering electrical modulation energy to a target tissue site ofthe patient at a programmed intensity value; an event detectorconfigured to automatically determine occurrences of an event during thetime period after initiating the sub-perception therapy; a sensorconfigured to sense evoked compound action potentials (eCAPs) in apopulation of neurons at the target tissue site in response to thedelivery of the electrical modulation energy; and a controller operablyconnected to the neurostimulator, the event detector and the sensor toautomatically respond to each of the occurrences of the event byperforming an automatic calibration process for the sub-perceptiontherapy to update the programmed intensity value accounting forenvironmental changes during the time period after initiating thesub-perception therapy, wherein the automatic calibration process thatis automatically performed in response to each of the occurrences of theevent during the time period includes automatically calibrating thesub-perception therapy to a perception threshold in response to each ofthe occurrences of the event, wherein the automatically calibrating thesub-perception therapy to the perception threshold includes:automatically detecting the perception threshold, by deliveringelectrical modulation energy using a series of incrementally increasingintensity values relative to the programmed intensity value to increasean intensity of the delivered electrical modulation energy to at leastthe perception threshold, and sensing at least one evoked compoundaction potential (eCAP) indicative of the perception threshold in apopulation of neurons at the target tissue site of the patient inresponse to the delivery of the electrical modulation energy at theseries of incrementally increasing intensity values; determining acorresponding intensity value from the series of incrementally increasedintensity values for the at least one sensed eCAP indicative of theperception threshold; determining a decreased intensity value based onthe corresponding intensity value; and updating the programmed intensityvalue for the electrical modulation energy using the decreased intensityvalue; wherein the controller is configured to control theneurostimulator to continue to deliver the sub-perception therapy duringthe time period by delivering electrical modulation energy to the targettissue site of the patient using the updated programmed intensity value.20. The system of claim 19, wherein the event is one of an identifiedphysical activity and/or posture, a user-initiated signal, a signalindicating migration of an electrode from which the electricalmodulation energy is delivered, and a predetermined periodicallyrecurring signal.